Dokument: The long non-coding RNA OTX2-AS1 promotes tumor growth and predicts response to BCL-2 inhibition in medulloblastoma
| Titel: | The long non-coding RNA OTX2-AS1 promotes tumor growth and predicts response to BCL-2 inhibition in medulloblastoma | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=68907 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250304-111448-2 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Qin, Nan [Autor] Paisana, Eunice [Autor] Picard, Daniel [Autor] Leprivier, Gabriel [Autor] Langini, Maike [Autor] Custódia, Carlos [Autor] Cascão, Rita [Autor] Conrad, Catleen [Autor] Peitzsch, Mirko [Autor] Stefanski, Anja [Autor] | |||||||
| Dateien: |
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| Stichwörter: | High-throughput drug screening, BCL-2 inhibitor, OTX2-AS1, Medulloblastoma, LncRNA | |||||||
| Beschreibung: | Purpose
Primary brain tumors are a leading cause of cancer-related death in children, and medulloblastoma is the most common malignant pediatric brain tumor. The current molecular characterization of medulloblastoma is mainly based on protein-coding genes, while little is known about the involvement of long non-coding RNAs (lncRNAs). This study aimed to elucidate the role of the lncRNA OTX2-AS1 in medulloblastoma. Methods Analyses of DNA copy number alterations, methylation profiles, and gene expression data were used to characterize molecular alterations of OTX2-AS1 in medulloblastoma tissue samples. In vitro analyses of medulloblastoma cell models and orthotopic in vivo experiments were carried out for functional characterization of OTX2-AS1. High-throughput drug screening was employed to identify pharmacological inhibitors, while proteomics and metabolomics analyses were performed to address potential mechanisms of drug action. Results We detected amplification and consecutive overexpression of OTX2 and OTX2-AS1 in a subset of medulloblastomas. In addition, OTX2-AS1 promoter methylation was linked to OTX2-AS1 expression. OTX2-AS1 knockout reduced medulloblastoma cell viability and cell migration in vitro and prolonged survival in the D283 orthotopic medulloblastoma mouse xenograft model. Pharmacological inhibition of BCL-2 suppressed the growth of OTX2-AS1 overexpressing medulloblastoma cells in vitro. Conclusions Our study revealed a pro-tumorigenic role of OTX2-AS1 in medulloblastoma and identified BCL-2 inhibition as a potential therapeutic approach to target OTX2-AS1 overexpressing medulloblastoma cells. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Qin, N., Paisana, E., Picard, D., Leprivier, G., Langini, M., Custódia, C., Cascão, R., Conrad, C., Peitzsch, M., Stefanski, A., Stühler, K., Fischer, U., Faria, C. C., Dietrich, S., Reifenberger, G., & Remke, M. (2023). The long non-coding RNA OTX2-AS1 promotes tumor growth and predicts response to BCL-2 inhibition in medulloblastoma. Journal of Neuro-Oncology, 165(2), 329–342. https://doi.org/10.1007/s11060-023-04508-y | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 04.03.2025 | |||||||
| Dateien geändert am: | 04.03.2025 |
